Hepatopathy, in which the destruction of hepatic cells progresses due to viruses or various toxic substances, may be an etiologic factor that causes acute or chronic hepatitis and, furthermore, liver cirrhosis, hepatoma etc. Specifically, in acute hepatitis subjective symptoms such as nausea, vomiting and malaise are more severe than in common hepatitis, and it is known to be associated with high fever, leukocytosis, and highly positive CRP, and jaundice may abruptly aggravate, sometimes leading to premature death. Even when premature death may be avoided, an extremely large number of cases that lead to cirrhosis or hepatoma are caused by chronic hepatitis, posing a social problem.
With respect to hepatitis by etiology, viruses (type A, type B, type C, type D, type E) are a predominant cause of acute hepatitis, and type C hepatitis among them accounts for the majority of cases of chronic liver diseases in Japan, accounting for as high as 90% of the causes of hepatoma. Hepatopathy caused by an autoimmune mechanism is called autoimmune hepatic diseases, which include primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and other related diseases in addition to autoimmune hepatitis.
Alcohol is primarily metabolized in the liver, and its chronic ingestion may affect various metabolic systems of the liver, causing hyperuricemia, hyperlipidemia, hyperlactemia and the like. The metabolic disorders of fatty acids may lead to the accumulation of neutral fats and the stimulation of inflammatory cells which may trigger hepatitis, and heavy drinking may lead to acute liver insufficiency, called severe alcoholic hepatitis, with a poor prognosis. The accumulation of fats in the liver cells is due to alcohol, caused by drinking, and hypernutrition, caused by obesity. Usually the accumulation of fats does not induce hepatitis, but may sometimes be associated with inflammation similar to alcoholic hepatitis, and some examples have been reported in which the disease progressed to cirrhosis.
Cirrhosis is a terminal stage of all chronic disorders of the liver and, through the repeated damage to, and regeneration of, hepatic cells, fibrosis occurs and regenerating nodules are formed throughout the entire liver. Accordingly, all hepatic diseases that exhibit chronic hepatic disorders cause the functional insufficiency of hepatic cells and portal hypertension. The etiology of about 400,000 patients with cirrhosis in Japan is predominantly virus-induced, among which hepatitis C virus accounts for 62% and hepatitis B virus for 15%. Virus-induced cirrhosis causes a high incidence of hepatoma and considerably affects the prognosis of cirrhosis as well. Other etiologies include alcohol, drugs and toxic substances, autoimmunity, cholestasis, circulatory disorders, metabolic anomalies, parasites, and the like.
As therapeutic regimens, the avoidance of causes is most important for diseases (alcohol-induced, drug-induced) for which the cause can be avoided. For virus-induced (HBV, HCV) diseases, the only therapeutic regimen available at present is interferon, but the effect is only minimal for HBV, and about 30-50% even for HCV. Recently, there were developments in which the combined use of lamivudine (antiviral agent) for type B hepatitis and ribavirin (antiviral agent) for type C hepatitis became available. On the other hand, for those cases in which viruses cannot be expelled, glucocorticoids, glycyrrhizin preparations, ursodeoxycholic acid etc. are only given for the purpose of slowing down hepatic disorders and the secondary or primary prevention of oncogenesis (Yakkyoku (The Journal of Practical Pharmacy), Vol. 54, Suppl., 2003). Thus, main therapies are ancillary liver supporting therapies, and there are no effective therapeutic agents for hepatitis or inhibitors for hepatitis induction without side effects (MEDICAL DIGEST, Vol. 39 (1), 1990).